mmg_233_2014_genetics_genomicsfandomcom-20200215-history
Histone Acetylation
Overview ]] Histones are small proteins located within a eukaryotic cell's nucleus which function in sorting and packaging DNA into nucleosomes. These proteins act as the central spools around which DNA winds, thus creating chromatin. Histone acetylation occurs when the lysine residues present on the N-terminus of the histone tails bind to an acetyl group that is taken from acetyl-coA by histone acetyltransferase (HAT) thus loosening the DNA in the nucleosome process and allowing for its transcription; while histone deacetylation occurs when histone deacetylase (HDAC) removes this acetyl group from the lysine and returns it to acetyl-coA, thus tightening the DNA strand and preventing transcription. These histone reactions occur after translation has occurred within the cell, and are reversible. Regulation Mechanism ]] Though the mechanism of histone acetylation was briefly outlined above, the full process is more complex than previously stated. Histone acetylation is the process in which the histone is chemically altered by the transfer of an acetyl functional group by histone acetyltransferases (HATs) from acetyl-coenzyme A to the NH3+ groups of the lysine amino acid residues within the N-terminal tail that protrudes from the histone core of the nucleosome complex. This process removes the positive charge normally assigned to the histones, causing the interactions between the histones within the affected N-terminus and the negatively charged phosphate groups of the DNA to decrease. This causes the highly condensed chromatin to loosen in the affected area due to weaker association between the binding components of the nuclosome. This unwinding of the chromatin allows DNA polymerase and other transcription factors to bind to this unraveled site, causing these genes to be transcribed and expressed. To undo this acetylation, histone deacetylace (HDACs) removes the acetyl group from the NH3+ group of the lysine along with one molecule of H2O, causing the histones to wrap the DNA tightly and prevent transcription. Stimuli affecting gene regulation Certain stimuli, such as high levels of stress, will cause an increase in the levels of acetylation for certain proteins. For example, in the tumor suppressor protein p53, high levels of cellular stress causes a significant increase in acetylation at it's three major sites: K164, K120 and the C terminus. If one of these sites is blocked, then the protein is still able to activate p21, another protein involved in cell cycle regulation (also known as cyclin-dependent kinase inhibitor 1). However, if all three sites are blocked, then p53 is unable to activate p21 and will lose its ability to suppress cellular growth. The acetylation of p53 is thought to be crucial in facilitating the protein's ability to trigger apoptosis. References Struhl, Kevin. "Histone Acetylation and Transcriptional Regulatory mechanisms." Genes & Development. Cold Spring Harbor Laboratory Press, 1998. Web. 19 Oct. 2014.. "Histone Acetylation and Genome Function." EpiGenie Epigenetics and NonCoding RNA News. Epigene, n.d. Web. 19 Oct. 2014. . Li, Qing et al. “Acetylation of Histone H3 Lysine 56 Regulates Replication-Coupled Nucleosome Assembly.” Cell 134.2 (2008): 244–255. PMC. Web. 4 Dec. 2014. Tang, Y., W. Zhao, Y. Chen, Y. Zhao, and W. Gu. "Result Filters." National Center for Biotechnology Information. U.S. National Library of Medicine, 27 June 2008. Web. 19 Oct. 2014. .